Before that, Wiest's major on-screen credits include Charlie Kaufman's Synecdoche, New York, A Guide to Recognizing Your Saints, Hannah and Her Sisters (Oscar ), The Purple Rose of Cairo, Radio Days, September, Bullets Over Broadway (Oscar ), Parenthood (Oscar nomination), Edward Scissorhands and The Birdcage.

Wiest also received an Emmy for The Road to Avonlea and for her performance in the HBO series In Treatment. On the stage, Wiest was most recently seen in The Cherry Orchard at Classic Stage Company, and before that, Arthur Miller's All My Sons on Broadway. Other New York theater appearances include The Seagull at Classic Stage Company, Wendy Wasserstein's Third, Memory House by Kathleen Tolan, Salome, Oedipus,The Shawl,Hunting Cockroaches,After the Fall,Beyond Therapy and The Art of Dining."